Smoking Cessation With Varenicline, a Selective α4β2 Nicotinic Receptor Partial Agonist: Results From a 7-Week, Randomized, Placebo- and Bupropion-Controlled Trial With 1-Year Follow-up

Background: Currently available smoking cessation therapies have limited success rates. Varenicline tartrate is a novel, selective nicotinic receptor partial agonist developed specifically for smoking cessation. This study evaluated the efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation. Bupropion hydrochloride was included as an active control. Methods: A phase 2, multicenter, randomized, doubleblind, placebo-controlled study of healthy smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3 mg once daily (n =1 28), 1.0 mg once daily (n=128), or 1.0 mg twice daily (n=127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion hydrochloride twice daily (n=128) for 7 weeks; or to placebo (n=127) for 7 weeks. Results: During the treatment phase, the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily (48.0%;P.001) and 1.0 mg once daily (37.3%;P.001), than for placebo (17.1%). Thebupropionratewas33.3%(P=.002vsplacebo).Thecarbon monoxide–confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate, 1.0 mg twice daily, group compared with the placebo group(14.4%vs4.9%;P=.002).Thebupropionratewas6.3%